Exploring Nociceptive Processing Differences 7.0. Project Summary/Abstract Native Americans (NAs) have a higher prevalence of pain than non-Hispanic whites and other U.S. minority groups. Yet, there is a lack of pain research in NAs, with only 28 papers on pain published in over 30 years. Moreover, no study has assessed pain processing to identify whether pain sensitivity (conscious pain experience), central sensitization (augmented pain signaling in the CNS), and/or CNS pain inhibition (descending pain modulation) contribute to this disparity. Our pilot data indicate that relative to non-Hispanic whites, NAs have lower pain sensitivity (e.g., higher pain tolerance) and show reduced central sensitization (reduced CNS response to pain) on a physiological measure (i.e., temporal summation of the nociceptive flexion reflex). This suggests their CNS responds differently to noxious input, which could have significant clinical implications. Specifically, being less pain sensitive may place NAs at risk for chronic pain because they could have difficulty detecting and preventing tissue damage and/or protecting tissue damage once it has occurred. However, results from these pilot data need to be replicated in a larger sample. Aim 1 will be to determine whether healthy, pain-free Native Americans (n=120) have lowered pain sensitivity, reduced central sensitization, and enhanced pain inhibitory processes relative to a non-Hispanic white control group (n=120). Testing will occur across two sessions using well-validated, state-of-the-art, quantitative sensory testing methods to assess pain processing from subjective (e.g., pain report) and physiological (nociceptive flexion reflex) pain outcomes. Pain sensitivity will be comprehensively assessed from pain threshold, tolerance, and report in response to multiple stimulus modalities (heat, cold, mechanical pressure, ischemia, electrocutaneous). Central sensitization will be assessed from: 1) temporal summation of heat pain (a subjective measure of sensitization), 2) nociceptive flexion reflex threshold (NFR, a physiological measure of spinal nociception), and 3) temporal summation of NFR (a physiological measure of spinal cord hyperexcitability). CNS inhibition of pain and NFR will be assessed from: 1) conditioned pain modulation (i.e., pain inhibits pain) and 2) emotional controls of nociception (i.e., pleasant emotions inhibit pain, unpleasant emotions enhance pain). Aim 2 is to identify individual differences that contribute to altered pain processing in NAs. Thus, pain coping (e.g., pain catastrophizing), sociocultural variables (e.g., ethnic identity), and heredity (i.e., blood quantu level) will be examined to determine whether they are associated with group differences in pain. This research is expected to impact minority health disparities in at least 5 ways: 1) identify mechanisms contributing to pain disparities in NAs, 2) determine if pain disparities in NAs result from physiological processes (e.g., CNS pain inhibition), 3) provide evidence that pain risk is physiologically different in NAs thus identifying the need for tailored interventions, 4) inform methods to assess NAs at-risk for chronic pain, and 5) promote interventions to eliminate pain disparity in NAs.